Tick-borne encephalitis in an immunocompromised patient

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Tick-borne encephalitis in an immunocompromised patient

Post by RitaA » Thu 10 Dec 2015 6:32

https://www.ntvg.nl/artikelen/tick-born ... d_abstract
‘Tick-borne’-encefalitis bij verminderde afweer
De ernstige gevolgen van een tekenbeet

Marienke de Bruijn, Netty van der Lely, Jan Marcelis en Gerwin Roks

‘Tick-borne’ encephalitis in an immunocompromised patient

This supplementary information is presented as submitted by the corresponding author. It has not been copy-edited by NTvG.


Tick-borne encephalitis virus (TBEV) is a flavivirus, mainly transmitted by ticks. The most important vectors are Ixodes ricinus (European subtype) and Ixodes persulcatus (Siberian and Far-Eastern subtypes). TBEV is endemic in East-Asia and a number of European countries. In the Netherlands it only occurs in travelers to endemic areas. Incubation period is 8 days (spreading from 4-28 days). Disease is biphasic; consisting of a non-specific first phase (malaise, fever, headache), latency phase of a few days, and a second phase with a variable course, from mild meningitis to lethal meningo-encephalo-radiculitis. There are no therapeutic options, only supportive treatment with control of symptoms. Vaccines are available.

Case description

A 48-year old woman, with medical history of systemic lupus erythematosus (SLE) and use of immunotherapy, presented with cough, fever and malaise since one day. Two weeks ago she had returned from a holiday to the Teutoburger wald, Germany. Because of suspected pneumonia she was treated with antibiotics and sent home. Two days later she presented with similar symptoms. She was admitted to the department of internal medicine. After two days the neurologist was consulted due to gait problems and ongoing headache. Neurologic examination showed gait instability and pain radiating from neck to left upper limb. Brain MRI was normal. Disease progressed with downbeat nystagmus and paresis of the left upper limb in 1 day. CSF analysis showed: mild mononuclear pleocytosis, decreased glucose and increased protein. Treatment with broad spectrum of antibiotics and aciclovir was started. Over 2 days she developed a tetraplegia and respiratory insufficiency. Differential diagnosis was meningo-radiculoencephalitis due to neuroborreliosis, flavivirus (West-Nile, TBEV) or autoimmune encephalitis. MRI was repeated with MR-angiography (MRA), showing hyperintens lesions in thalamus and caudate nucleus on FLAIR images. The patient was transmitted to the intensive care unit and intubated. Due to probable calibre changes on MRA and rash on the patient’s hands noticed by relatives the diagnosis of SLE cerebral vasculitis was made and treatment with immunotherapy was started. Eventually, through normal MRA, after revision, and normal anti-ds-DNA titer, this diagnosis was rejected. Immunotherapy was tapered. Later on, serologic tests showed positive IgM and IgG for TBEV with increasing titer in the following days. The diagnosis of TBEV meningo-radiculoencephalitis was made. Unfortunately, after more than 90 days of intensive treatment, the patient died of respiratory insufficiency due to a pneumonia.


This case shows the difficulties in distinguishing viral encephalitis from cerebral vasculitis. The diagnosis TBEV is based on clinical characteristics, radiological abnormalities and CSF findings. Additional serological tests (raised TBEV IgG and IgM) confirm the diagnosis of TBEV.

It is important to think of TBE when it concerns patients who have traveled to endemic areas and present with meningitis, encephalitis and/or radiculitis. TBE can have a rapidly progressive, severe and sometimes lethal course, it is recommended to vaccinate travelers visiting these areas, especially if immunocompromised. Because of lower antibody titer compared to healthy individuals it is recommended to monitor the antibody titer in immunocompromised patients.

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Re: Tick-borne encephalitis in an immunocompromised patient

Post by RitaA » Thu 10 Dec 2015 6:45

http://wwwnc.cdc.gov/travel/yellowbook/ ... cephalitis
Tickborne Encephalitis

Marc Fischer, Ingrid B. Rabe, Pierre E. Rollin


Tickborne encephalitis (TBE) virus is a single-stranded RNA virus that belongs to the genus Flavivirus. TBE virus has 3 subtypes: European, Siberian, and Far Eastern.


TBE virus is transmitted to humans through the bite of an infected tick of the Ixodes species, primarily I. ricinus (European subtype) or I. persulcatus (Siberian and Far Eastern subtypes). The virus is maintained in discrete areas of deciduous forests. Ticks act as both vector and virus reservoir, and small rodents are the primary amplifying host. TBE can also be acquired by ingesting unpasteurized dairy products (such as milk and cheese) from infected goats, sheep, or cows. TBE virus transmission has infrequently been reported through laboratory exposure and slaughtering viremic animals. Direct person-to-person spread of TBE virus occurs only rarely, through blood transfusion or breastfeeding.


TBE is endemic in focal areas of Europe and Asia, extending from eastern France to northern Japan and from northern Russia to Albania. Approximately 5,000‒13,000 TBE cases are reported each year, with large annual fluctuations. Russia has the largest number of reported cases. The highest disease incidence has been reported from western Siberia and the Baltic States (Estonia, Latvia, Lithuania). Other European countries with reported cases or known endemic areas include Albania, Austria, Belarus, Bosnia, Croatia, Czech Republic, Denmark, Finland, France, Germany, Hungary, Italy, Norway, Poland, Romania, Serbia, Slovakia, Slovenia, Sweden, Switzerland, and Ukraine. Asian countries with reported TBE cases or virus activity include China, Japan, Kazakhstan, Kyrgyzstan, Mongolia, and South Korea.

Most cases occur from April through November, with peaks in early and late summer when ticks are active. The incidence and severity of disease are highest in people aged ≥50 years. Most cases occur in areas <2,500 ft (750 m). In the last 30 years, the geographic range of TBE virus appears to have expanded to new areas, and the virus has been found at altitudes up to and above 5,000 ft (1,500 m). These trends are likely due to a complex combination of changes in diagnosis and surveillance, human activities and socioeconomic factors, and ecology and climate.

The overall risk of acquiring TBE for an unvaccinated visitor to a highly endemic area during the TBE virus transmission season has been estimated at 1 case per 10,000 person-months of exposure. Most TBE virus infections result from tick bites acquired in forested areas through activities such as camping; hiking; fishing; bicycling; collecting mushrooms, berries, or flowers; and outdoor occupations such as forestry or military training. The risk is negligible for people who remain in urban or unforested areas and who do not consume unpasteurized dairy products.

Vector tick population density and infection rates in TBE virus-endemic foci are highly variable. For example, TBE virus infection rates in I. ricinus in central Europe vary from <0.1% to approximately 5%, depending on geographic location and time of year, while rates of up to 40% have been reported in I. persulcatus in Siberia. The number of TBE cases reported from a country depends on the ecology and geographic distribution of TBE virus, the intensity of diagnosis and surveillance, and the vaccine coverage in the population. Therefore, the number of human TBE cases reported from an area may not be a reliable predictor of a traveler’s risk for infection. The same ticks that transmit TBE virus can also transmit other pathogens, including Borrelia burgdorferi (the agent for Lyme disease), Anaplasma phagocytophilum (anaplasmosis), and Babesia spp. (babesiosis), and simultaneous infection with multiple organisms has been described.

From 2000 through 2011, 5 cases of TBE among US travelers to Europe and China were reported. TBE is not a nationally notifiable disease in the United States, and additional cases may have occurred.


Approximately two-thirds of infections are asymptomatic. The median incubation period for TBE is 8 days (range, 4–28 days). The incubation period for milkborne exposure is usually shorter (3–4 days). Acute neuroinvasive disease is the most commonly recognized clinical manifestation of TBE virus infection. However, TBE disease often presents with milder forms of the disease or a biphasic course:

o First phase: nonspecific febrile illness with headache, myalgia, and fatigue. Usually lasts for several days and may be followed by an afebrile and relatively asymptomatic period. Up to two-thirds of patients may recover without any further illness.

o Second phase: central nervous system involvement resulting in aseptic meningitis, encephalitis, or myelitis. Findings include meningeal signs, altered mental status, cognitive dysfunction, ataxia, rigidity, seizures, tremors, cranial nerve palsies, and limb paresis.

Disease severity increases with age. Although TBE tends to be less severe in children, residual symptoms and neurologic deficits have been described. Clinical course and long-term outcome also vary by TBE virus subtype:

o The European subtype is associated with milder disease, a case-fatality ratio of <2%, and neurologic sequelae in up to 30% of patients.
o The Far Eastern subtype is often associated with a more severe disease course, including a case-fatality ratio of 20%–40% and higher rates of severe neurologic sequelae.
o The Siberian subtype is more frequently associated with chronic or progressive disease and has a case-fatality ratio of 2%–3%.


TBE should be suspected in travelers who develop a nonspecific febrile illness that progresses to neuroinvasive disease within 4 weeks of arriving from an endemic area. A history of tick bite may be a clue to this diagnosis; however, approximately 30% of TBE patients do not recall a tick bite.

Serology is typically used for laboratory diagnosis. IgM-capture ELISA performed on serum or cerebrospinal fluid is virtually always positive during the neuroinvasive phase of the illness. Vaccination history, date of onset of symptoms, and information regarding other flaviviruses known to circulate in the geographic area that may cross-react in serologic assays need to be considered when interpreting results. During the first phase of the illness, TBE virus or viral RNA can sometimes be detected in serum samples by virus isolation or RT-PCR. However, by the time neurologic symptoms are recognized, the virus or viral RNA is usually undetectable. Therefore, virus isolation and RT-PCR should not be used to rule out a diagnosis of TBE. Clinicians should contact their state or local health department, the CDC Viral Special Pathogens Branch (404-639-1115), or CDC Division of Vector-Borne Diseases (970-221-6400) for assistance with diagnostic testing.


There is no specific antiviral treatment for TBE; therapy consists of supportive care and management of complications.


Personal Protection Measures

Travelers should avoid consuming unpasteurized dairy products and use all measures to avoid tick bites (see Chapter 2, Protection against Mosquitoes, Ticks, & Other Arthropods).


No TBE vaccines are licensed or available in the United States. Two inactivated cell culture-derived TBE vaccines are available in Europe, in adult and pediatric formulations: FSME-IMMUN (Baxter, Austria) and Encepur (Novartis, Germany). The adult formulation of FSME-IMMUN is also licensed in Canada. Two other inactivated TBE vaccines are available in Russia: TBE-Moscow (Chumakov Institute, Russia) and EnceVir (Microgen, Russia). Immunogenicity studies suggest that the European and Russian vaccines should provide cross-protection against all 3 TBE virus subtypes. At least 1 other TBE vaccine is produced in China, but information regarding this vaccine is not available in the English literature.

For both FSME-IMMUN and Encepur, the primary vaccination series consists of 3 doses. The specific recommended intervals between doses vary by country and vaccine (Table 3-19). Although no formal efficacy trials of these vaccines have been conducted, indirect evidence suggests that their efficacy is >95%. Vaccine failures have been reported, particularly in people aged ≥50 years.

Because the routine primary vaccination series requires ≥6 months for completion, most travelers to TBE-endemic areas will find avoiding tick bites to be more practical than vaccination. However, an accelerated vaccination schedule has been evaluated for both European vaccines, and results in seroconversion rates are similar to those observed with the standard vaccination schedule. Travelers anticipating high-risk exposures, such as working or camping in forested areas or farmland, adventure travel, or living in TBE-endemic countries for an extended period of time, may wish to be vaccinated in Canada or Europe.

CDC website: http://www.cdc.gov/vhf/tbe


Page created: July 10, 2015
Page last updated: July 10, 2015
Page last reviewed: July 10, 2015

Posts: 2768
Joined: Thu 1 Jul 2010 8:33

Re: Tick-borne encephalitis in an immunocompromised patient

Post by RitaA » Thu 10 Dec 2015 7:06

World J Clin Cases. 2015 May 16; 3(5): 430–441.
Published online 2015 May 16. doi: 10.12998/wjcc.v3.i5.430
PMCID: PMC4419106

Tick-borne encephalitis: A review of epidemiology, clinical characteristics, and management

Petra Bogovic, Franc Strle, Department of Infectious Diseases, University Medical Center Ljubljana, 1525 Ljubljana, Slovenia


Tick-borne encephalitis is an infection of central nervous system caused by tick-borne encephalitis virus transmitted to humans predominantly by tick bites. During the last few decades the incidence of the disease has been increasing and poses a growing health problem in almost all endemic European and Asian countries. Most cases occur during the highest period of tick activity, in Central Europe mainly from April to November. Tick-borne encephalitis is more common in adults than in children. Clinical spectrum of the disease ranges from mild meningitis to severe meningoencephalitis with or without paralysis. Rare clinical manifestations are an abortive form of the disease and a chronic progressive form. A post-encephalitic syndrome, causing long-lasting morbidity that often affects the quality of life develops in up to 50% of patients after acute tick-borne encephalitis. Clinical course and outcome vary by subtype of tick-borne encephalitis virus (the disease caused by the European subtype has milder course and better outcome than the disease caused by Siberian and Far-Easter subtypes), age of patients (increasing age is associated with less favorable outcome), and host genetic factors. Since clinical features and laboratory results of blood and cerebrospinal fluid are nonspecific, the diagnosis must be confirmed by microbiologic findings. The routine laboratory confirmation of the tick-borne encephalitis virus infection is based mainly on the detection of specific IgM and IgG antibodies in serum (and cerebrospinal fluid), usually by enzyme-linked immunosorbent assay. There is no specific antiviral treatment for tick-borne encephalitis. Vaccination can effectively prevent the disease and is indicated for persons living in or visiting tick-borne encephalitis endemic areas.

Keywords: Tick-borne encephalitis, Diagnosis, Epidemiology, Clinical manifestations, Treatment, Prevention/vaccination
Core tip: Tick-borne encephalitis (TBE) is the most common tick-borne central nervous system infection in Europe and Asia. It is caused by three subtypes of TBE virus: European, Siberian and Far-Eastern. Because of relatively severe clinical course, the absence of etiologic treatment, considerable proportion of patients with incomplete recovery after acute illness, as well as due to increasing incidence it represents a growing public health problem that could be substantially reduced with vaccination.
The full article continues in the link above. Here are a few snippets:
With increasing of tourism, TBE has become a more global problem. Therefore, it should be included in the differential diagnosis of the central nervous system infections not only for those living within an endemic region but-in case of an appropriate epidemiological history-also in patients living outside endemic areas.
Post-encephalitic syndrome

TBE may cause long-lasting morbidity which often has an impact on patients’ quality of life and, sometimes, necessitates an alteration of lifestyle. Many nonspecific neurological/neuropsychiatric symptoms and residual neurological dysfunctions have been reported in some prospective and several retrospective studies, but findings are hard to compare due to diverse study designs, distinct definitions, and variable follow-up times. Most studies also failed to comprise a control group; as a result findings are difficult to interpret because of unclear distinctions between post-encephalitic syndrome, other sequelae of TBE, and symptoms present in general population. Published data suggest that 40% to 50% of patients after acute TBE develop a post-encephalitic syndrome[46]. The most frequently reported symptoms have been cognitive disorders, neuropsychiatric complaints (such as apathy, irritability, memory and concentration disorders, altered sleep pattern), headache, hearing loss and/or tinnitus, disturbances of vision, balance and coordination disorders, and flaccid paresis or paralysis[24,37,38,47-49].

The differential diagnosis of TBE is extensive and includes a wide variety of central nervous system infections due to other infectious agents as well as noninfectious diseases.

In the initial, viremic phase of TBE, when a patient present with fever, headache, arthralgia, myalgia, and malaise the differential diagnosis may include various viral syndromes; if nausea, vomiting, diarrhea, and anorexia are present, gastroenteritis is a possible explanation. When signs and symptoms of central nervous system involvement develop, TBE needs to be differentiated from encephalitis or aseptic meningitis due to many other viruses. Differential diagnosis comprises also other tick-borne diseases such as Lyme borreliosis, babesiosis, human granulocytic anaplasmosis, tick-transmitted rickettsioses, and tularemia[20].

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